Primary results from TAIL: a global single-arm safety study of atezolizumab monotherapy in a diverse population of patients with previously treated advanced non-small cell lung cancer

Abstract

Background: Atezolizumab treatment improves survival, with manageable safety, in patients with previously treated advanced/metastatic non-small cell lung cancer. The global phase III/IV study TAIL (NCT03285763) was conducted to evaluate the safety and efficacy of atezolizumab monotherapy in a clinically diverse population of patients with previously treated non-small cell lung cancer, including those not eligible for pivotal trials.

Methods: Patients with stage IIIB/IV non-small cell lung cancer whose disease progressed after 1-2 lines of chemotherapy were eligible for this open-label, single-arm, multicenter study, including those with severe renal impairment, an Eastern Cooperative Oncology Group performance status of 2, prior anti-programmed death 1 (PD-1) therapy, and autoimmune disease. Atezolizumab was administered intravenously (1200 mg every 3 weeks). Coprimary endpoints were treatment-related serious adverse events and immune-related adverse events.

Results: 619 patients enrolled and 615 received atezolizumab. At data cutoff, the median follow-up was 12.6 months (95% CI 11.9 to 13.1). Treatment-related serious adverse events occurred in 7.8% and immune-related adverse events in 8.3% of all patients and as follows, respectively, in these subgroups: renal impairment (n=78), 11.5% and 12.8%; Eastern Cooperative Oncology Group performance status of 2 (n=61), 14.8% and 8.2%; prior anti-PD-1 therapy (n=39), 5.1% and 7.7%; and autoimmune disease (n=30), 6.7% and 10.0%. No new safety signals were reported. In the overall population, the median overall survival was 11.1 months (95% CI 8.9 to 12.9), the median progression-free survival was 2.7 months (95% CI 2.1 to 2.8) and the objective response rate was 11%.

Conclusions: This study confirmed the benefit-risk profile of atezolizumab monotherapy in a clinically diverse population of patients with previously treated non-small cell lung cancer. These safety and efficacy outcomes may inform treatment decisions for patients generally excluded from checkpoint inhibitor trials.

Keywords: PD-L1 inhibitor; checkpoint inhibitor; clinical trials; immunotherapy; lung neoplasms; metastatic; phase IIII clinical trial; subgroup analysis.

Figure 1

Trial profile and patient disposition. AE, adverse event.

Figure 2

Primary endpoint: most common treatment-related SAEs and irAEs (in ≥2 patients) by CTCAE grade. (A) Treatment-related SAEs and (B) treatment-related irAEs. ^aAdverse events were defined as serious if they were fatal, were life threatening, required hospitalization, resulted in disability, or resulted in a congenital birth defect in an infant born to a mother exposed to study drug. ^birAEs were defined as any adverse event of special interest requiring corticosteroid treatment within 30 days of onset. ALT, alanine aminotransferase; AST, aspartate aminotransferase; CTCAE, Common Terminology Criteria for Adverse Events; irAEs, immune-related adverse events; IRR, infusion-related reaction; SAE, serious adverse event.

Figure 3

Incidence of treatment-related SAEs and irAEs in key subgroups. (A) treatment-related SAEs and (B) treatment-related irAEs. The Clopper–Pearson method was used to calculate the 95% CI. ^aRenal impairment defined as estimated glomerular filtration rate <60 mL/min/1.73 m². CNS, central nervous system; ECOG PS, Eastern Cooperative Oncology Group performance status; HBV/HCV, hepatitis B/C virus; irAE, immune-related adverse event; PD-1, programmed death-1; SAE, serious adverse event.